# Severe Rectal Syphilis in the Setting of Profound HIV Immunosuppression: A Case Report Highlighting ERG/CD38 Immunophenotyping and a Review of the Literature

## TL;DR

This case report describes a rare and severe case of syphilitic proctitis in an HIV patient with very low CD4 levels, highlighting the use of ERG/CD38 immunophenotyping for accurate diagnosis.

## Contribution

The paper presents one of the first cases of syphilitic proctitis in an HIV patient with CD4 < 50 cells/µL and demonstrates the utility of ERG/CD38 immunophenotyping in diagnosis.

## Key findings

- ERG and CD38 immunophenotyping helped distinguish syphilitic proctitis from inflammatory or neoplastic conditions.
- Syphilitic proctitis in profound HIV immunosuppression can present with atypical features and rapid progression.
- Combining radiology, histopathology, and serology enables timely diagnosis and treatment to prevent complications like neurosyphilis.

## Abstract

Background and Aim: Syphilis, caused by Treponema pallidum, classically presents with genital or anal chancres; rectal involvement is rare and frequently misdiagnosed as inflammatory bowel disease or malignancy. We describe an unusually severe case of syphilitic proctitis in the setting of advanced HIV-related immunosuppression (CD4 39 cells/µL), in which targeted immunophenotyping (ERG and CD38) was a valuable adjunctive tool in the differential diagnosis. Case Presentation: A 46-year-old man with a recent history of erosive gastritis and esophageal candidiasis presented after six months of unintentional 20 kg weight loss, profound fatigue, intermittent fevers, profuse diarrhea, and two episodes of hematemesis. Workup revealed a new diagnosis of HIV infection (CD4: 39 cells/µL; viral load: 87,837 copies/mL). Contrast-enhanced CT demonstrated uniform, concentric rectal wall thickening (“target sign”). Colonoscopic biopsy showed exuberant granulation tissue and dense plasma cell infiltrates. Immunohistochemistry revealed a dense infiltrate of CD38-positive plasma cells and ERG-positive endothelial proliferation. These findings, in the context of positive serology, were highly supportive of a spirochetal etiology and helped differentiate it from potential mimics. Serology was positive for latent late syphilis (VDRL 1:64). The patient received three weekly doses of intramuscular benzathine penicillin; lumbar puncture excluded neurosyphilis. Discussion: This is among the first reported cases of syphilitic proctitis in a patient with CD4 < 50 cells/µL, where advanced immunophenotyping differentiated syphilitic inflammation from neoplastic or inflammatory mimics. Profound immunosuppression accelerates disease progression and yields atypical clinical features. Conclusion: In HIV-infected patients with chronic rectal symptoms, especially those with CD4 < 50 cells/µL, syphilitic proctitis must be considered. Integration of radiologic assessment, histopathology with ERG/CD38 staining, and serologic testing permits prompt diagnosis. Early benzathine penicillin therapy and rigorous clinical and serologic follow-up are essential to prevent complications, including neurosyphilis.